The Duke of Cambridge has questioned why legal highs are available and spoken of being called out in his rescue pilot role to help users.
William's comments came as he spent the day in Dundee with Kate highlighting services, charities and organisations supporting young people with mental health problems.
Since June the Duke has been flying missions as a helicopter pilot with East Anglian Air Ambulance, a role that will have seen the royal and his crewmates called to a range of emergencies.
When the Cambridges visited a centre providing drop-in and other facilities for young people, he spoke with members of a regional organisation called Body Matters and told them: ''I don't know why there are legal highs.
''We have been called out when people are having fits or cardiac arrests after taking them.''
Addiction youth worker Alain Saum said she now does outreach work at all nine of the city's high schools because the problem is so widespread.
''It is a big concern in Dundee. People who wouldn't normally do drugs take them because of the word legal,'' she said.
''And a small packet might contain 50 doses but people take it all at once.''
The Duke also spoke out about the nation's attitude to mental health, saying it was "sad" that "society does not seem to listen enough" to those with problems.
William's statement came as he and Kate sat down with a group of young people at Dundee Rep theatre who spoke openly about their battles with mental health issues and their work helping others.
In recent weeks the royal couple have been focusing their public work on promoting the emotional and psychological wellbeing of children and teenagers and visited Dundee for the first time officially to learn more about how the area is dealing with the issue.
The visit began on a lighter note with the Duke and Duchess spending Thursday night at the nearby town of St Andrews where they went to university, met and fell in love more than a decade ago.
They stayed at The Old Course Hotel, an exclusive resort and spa overlooking one of the world's most famous golf courses.
Before walking into the Rep theatre the royal couple went on a brief walkabout outside and the Duchess confessed to one well-wisher in the crowds that she was not thrilled by the Duke riding his powerful motorbike.
Fearghas Simpson, 28, a recruitment executive from Ayr, asked Kate, who wore an outfit featuring a kilt by Scottish designer Christopher Kane, if William was still riding his motorbike.
He said she replied: "He's still riding it. It always fills me with horror when he goes out on it - I'm terrified. Hopefully, I'm going to keep George off it."
A group of young volunteers with See Me, a Scotland-wide initiative to end mental health stigma, discussed their experiences of the issue and how they were helping others when they sat down with the Cambridges at the theatre.
During the chat William told the group of eight young people and senior staff from See Me: "It seems to me sad that society does not seem to listen enough, all the suggestions here and all the evidence you're giving us is very much that society doesn't seem to listen.
"And yet it's the most basic fundamental point of families and communities, whatever to listen to each other.
"And so I think what this mental health piece will do, will be able to really raise everyone's awareness, that we should just stop and listen and take a note of what's around us and those around us and pay more attention.
"And hopefully that will help more people come forward."
Before leaving the couple visited explorer Captain Scott's ship RRS (Royal Research Ship) Discovery, which was built in Dundee and carried him - and a young Ernest Shackleton - on their first expedition to Antarctica in 1901.
And they showed off their competitive streaks when they played computer games created by a group of young Bafta award winners.